Angiotensin converting enzyme (ACE) is an enzyme that acts on angiotensin I which is generated from angiotensinogen by digestion with renin and converts it to angiotensin II by releasing two amino acids in the C-terminal thereof. The angiotensin converting enzyme not only acts on producing angiotensin II that has a strong hypertensive effect but also acts on inactivating bradykinin that has a hypotensive effect. From those actions, angiotensin converting enzyme inhibitors have been used as therapeutic agents for hypertension, and, for example, Captopril (produced by Sankyo Co., Ltd.) and Renivase (produced by Banyu Pharmaceutical Co., Ltd.) have been known as commercially available drugs. In addition, it is also known that the angiotensin converting enzyme inhibitors have an effect of making cardiac hypertrophy regress.
On the other hand, peptides having angiotensin converting enzyme inhibitory effects have been found in natural products or in enzyme-degraded products of animal proteins such as casein and gelatin, vegetable proteins such as those from wheat, rice and corn, and fish proteins such as those from sardine. For instance, the known peptides found in natural products include teprotide (nonapeptide, SQ20881) and metabolite IS83 of Actinomyces bacterium belonging to the genus Streptomyces (JP 58-177920 A). In addition, the known enzyme-degraded products include peptides obtained by decomposing casein with trypsin (JP 58-109425 A, JP 59-44323 A, JP 59-44324 A, JP 61-36226 A, and JP 61-36227 A), peptides obtained by hydrolyzing casein with thermolysin (JP 6-277090 A, JP 6-277091 A, JP 6-279491A, JP 7-101982A, and JP 7-101985A), peptides obtained by hydrolyzing casein or the like with lactic bacteria or a combination of proteinases and peptidases (JP 6-197786 A, JP 6-40944 A, and JP 2001-136995 A (which are hereinafter referred to as “References 1 to 3”, respectively) The peptides of References 1 to 3 are used as foods for specified health use having the hypotensive effect.
Among the peptides described above, the peptide described in JP 7-101982 A (hereinafter, referred to as “Reference 4”) shows the highest inhibitory activity against angiotensin converting enzyme and has a comparatively simple structure of tripeptide.